We have developed monoclonal antibodies (MoAbs) that reveal the heterogeneity of MHC class II antigens expression on normal mononuclear cells. Recently, we have found preliminary evidence that leukemic cells selectively express distinct class II antigens. Initial molecular characterization of the class II polygenic complex suggests the possibility of sequential and/or combinatorial gene expression. Our hypothesis is that the heterogeneity of class II antigens expressed on normal cells reflects the different lineages of cells expressing these antigens. Furthermore, the selective expression of class II antigens on leukemic cells is the phenotypic correlate of independent, noncoordinate gene expression associated with cellular differentiation. To test this hypothesis, a library of murine MoAbs to distinct monomorphic class II epitopes will be used to probe the heterogeneity of class II antigens on resting and activated mononuclear cells from normal donors, as well as on acute and chronic leukemic cells. We will investigate the capacity of leukemic cells to present antigen, to stimulate allogeneic T cell proliferation, and to induce the generation of cytotoxic T cells and thus correlate the functional potential of the leukemic cell with its expression of class II molecules. The relationship of the genes coding for the molecules identified by our MoAbs to the DR, DC, and SB class II gene products will be determined by analysis of radiation-induced MHC mutants. Finally, class II antigens synthesized by leukemic cells will be used to generate MoAbs that react with class II antigens on cells at an early stage of differentiation. (AG)